Strategies to alleviate or mitigate cognitive deficits with pharmaceutical, educational, and behavioral interventions have received significant attention recently. New methods for improving the lives of those with intellectual disabilities, age-related cognitive decline, and other forms of learning disability by reinforcing and/or consolidating memory and cognitive function are desired. Moreover, healthy, typically-developed students of all ages would benefit from a method for enhancing memory consolidation and thus long-term memory retention.
Sleep has many inherent benefits, including an important role in memory consolidation. Brain rhythms regulate information processing in different states to enable learning and memory formation.
The sleep begins with light sleep (stage I and stage II) which leads quickly to slow-wave sleep (SWS) state (stages 3 and 4). After about 90 minutes, rapid eye movement (REM) sleep appears. These stages are the first sleep cycle. A cycle lasts about 90 minutes. One night has 4 to 6 cycles, depending on the duration of sleep. The first half of sleep is particularly rich in deep sleep, while the second half is essentially constituted by alternating light sleep and REM sleep.
SWS is thought to be critical for many of sleep's restorative effects (Cirelli C, Tononi G 2008 PLoS Biol 6(8): e216). In particular, many convergent experimental findings suggest that sleep slow oscillations (SO, <1 Hz) in the electroencephalogram (EEG), characterized by global up-states (neuronal firing) and down-states (neuronal silence), can promote synaptic downscaling and plasticity and, consequently, may play an active role in learning and memory consolidation (Steriade M, et al 1993 Science 262(5134):679-85; Tononi, G and Cirelli, C 2006 Sleep Med. Rev. 10, 49-62). In this context, stimuli, in addition to induce evoked-potentials, can affect EEG activity by boosting various sleep brain rhythms and, thus, could provide a tool to artificially improve SO generation (Tononi, G., et al 2010 Medicamundi 54, 73-79). Nevertheless, previous studies imposed simulations on the brain disregarding the phase of ongoing endogenous oscillating activity, which might explain the overall limited enhancement in SO induction (patent applications: WO2012/138761, WO2014/028372).
In addition, a precedent study already tried to stimulate in phase with SO but no increase in SO events was observed nor differences in sleep architecture (Ngo H V, et al. 2013 Neuron 78, 545-553).
Surprisingly, the new method disclosed herein is able to initiate and enhance SO by presenting stimuli (tones, lights, tactile stimulation on the body surface) in synchrony with the brain's own rhythm. More surprisingly the sleep architecture of the subject is modified.